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Subarachnoid HemorrhageNCT04557618

Auricular VNS Following Subarachnoid Hemorrhage

A study testing Auricular Vagus Nerve Stimulation in people with Subarachnoid Hemorrhage, run by Anna Huguenard at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following spontaneous subarachnoid hemorrhage. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Subarachnoid Hemorrhage
What is being tested?
Auricular Vagus Nerve Stimulation
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteUnited States
Study dates
5 Jan 2021to 15 Mar 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Spontaneous subarachnoid hemorrhage

Who cannot join

  • Trauma-induced subarachnoid hemorrhage
  • Ongoing chemotherapy
  • Taking immunosuppressive medications for other medical illnesses
  • Presence of a pacemaker
  • Prolonged bradycardia at time of admission

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Transcutaneous Auricular Vagus Nerve Stimulation Following Spontaneous Subarachnoid Hemorrhage

This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following spontaneous subarachnoid hemorrhage.

Read the detailed description

Vagal nerve stimulation (VNS) has been studied in several inflammatory conditions, and has been implemented in animal models of subarachnoid hemorrhage (SAH) with promising results. The purpose of the proposed study is to determine how applying auricular VNS in patients presenting with spontaneous SAH impacts their expression of inflammatory markers in their blood and cerebrospinal fluid (CSF), and how it impacts their clinical course and outcomes.

This study will involve randomizing patients to stimulation with VNS, or sham stimulation. Blood and CSF will be collected on admission, and serially throughout the patient's admission. Clinical events tracked during the hospital stay include development of cerebral vasospasm, need for CSF diversion via a shunt, stress-induced cardiomyopathy, and development of stroke or global cerebral ischemia. Outcomes following admission will include functional scores at discharge, and at follow-up visits for up to 2 years after discharge.

Being tested
Auricular Vagus Nerve Stimulation, Sham Auricular Vagus nerve Stimulation
Keywords
Vagal nerve stimulation
Medical subject headings
Subarachnoid Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Auricular Vagus Nerve StimulationDevice

    Transcutaneous auricular vagal nerve stimulation

  • Sham Auricular Vagus nerve StimulationDevice

    Transcutaneous auricular vagal nerve ear clip applied without current

Study groups in NCT04557618
Study groupRoleWhat they receive
Auricular VNS StimulationExperimentalParticipants receive twice daily auricular vagal nerve stimulation
Receives: Device: Auricular Vagus Nerve Stimulation
Sham Auricular VNS StimulationSham comparatorParticipants will have an auricular vagal nerve stimulator applied twice daily, without the stimulation applied
Receives: Device: Sham Auricular Vagus nerve Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Inflammatory markers in the serum on admission

    TNF alpha from blood draw

    Measured: On hospital day 1

  2. Change in inflammatory markers in the serum

    TNF alpha from blood draws

    Measured: Through hospital admission, average of 4 weeks

  3. Inflammatory markers in the CSF on admission

    TNF alpha from cerebrospinal fluid

    Measured: On hospital day 1

  4. Change in inflammatory markers in the CSF

    TNF alpha from cerebrospinal fluid

    Measured: Through hospital admission, average of 4 weeks

  5. Cerebral vasospasm

    Presence of moderate/severe radiographic vasospasm

    Measured: Through hospital admission, average of 4 weeks

  6. Hydrocephalus

    Need for permanent CSF diversion via a ventricular shunt

    Measured: Through hospital admission, average of 4 weeks

Secondary outcomes (9)

  1. Inflammatory markers in the serum on admission

    IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8from blood draws

    Measured: On hospital day 1

  2. Change in inflammatory markers in the serum

    IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8 from blood draws

    Measured: Through hospital admission, average of 4 weeks

  3. Inflammatory markers in the CSF on admission

    IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, from cerebrospinal fluid

    Measured: On hospital day 1

  4. Change in inflammatory markers in the CSF

    IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, from cerebrospinal fluid

    Measured: Through hospital admission, average of 4 weeks

  5. Cerebral vasospasm

    Additional features of vasospasm: 1) Number of vascular studies obtained, 2) Need for blood pressure augmentation or hypervolemia, 3) Need for intraarterial or intrathecal vasodilator, 4) Need for angioplasty

    Measured: Through hospital admission, average of 4 weeks

  6. Cerebral ischemia

    Presence of cerebral ischemia based on the following criteria: Radiographic evidence of a new infarct or stroke

    Measured: Through hospital admission, average of 4 weeks

  7. Hydrocephalus

    Duration of temporary CSF diversion via an external ventricular drain

    Measured: Through hospital admission, average of 4 weeks

  8. Clinical outcome

    Modified Rankin Scale for Neurological Disability (minimum score 0, maximum score 6, better outcomes have lower scores)

    Measured: 2 years

  9. Stressed-induced cardiomyopathy

    Presence of stressed-induced cardiomyopathy based on any of the following criteria: 1) New troponin elevation, 2) New EKG changes (specifically ST segment elevation, ST segment depression, left bundle branch block, prolonged QT interval), 3) New findings of cardiomyopathy on echocardiogram

    Measured: Through hospital admission, average of 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2020
  2. Study start5 Jan 2021
  3. Primary completion15 Mar 2026
  4. Study completion15 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants are assigned to either stimulation or sham stimulation arms
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04557618
Sponsor's protocol ID
202007034
Status last verified
Oct 2026
First submitted
4 Sep 2020
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tan G, Huguenard AL, Donovan KM, Demarest P, Liu X, Li Z, Adamek M, Lavine K, Vellimana AK, Kummer TT, Osbun JW, Zipfel GJ, Brunner P, Leuthardt EC. The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial. Elife. 2025 Jan 9;13:RP100088. doi: 10.7554/eLife.100088.

    PubMed 39786346

  • Huguenard A, Tan G, Johnson G, Adamek M, Coxon A, Kummer T, Osbun J, Vellimana A, Limbrick D Jr, Zipfel G, Brunner P, Leuthardt E. Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial. PLoS One. 2024 Aug 23;19(8):e0301154. doi: 10.1371/journal.pone.0301154. eCollection 2024.

    PubMed 39178291

  • Huguenard AL, Tan G, Rivet DJ, Gao F, Johnson GW, Adamek M, Coxon AT, Kummer TT, Osbun JW, Vellimana AK, Limbrick DD, Zipfel GJ, Brunner P, Leuthardt EC. Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial. medRxiv [Preprint]. 2024 May 1:2024.04.29.24306598. doi: 10.1101/2024.04.29.24306598.

    PubMed 38746275

  • Tan G, Huguenard AL, Donovan KM, Demarest P, Liu X, Li Z, Adamek M, Lavine K, Vellimana AK, Kummer TT, Osbun JW, Zipfel GJ, Brunner P, Leuthardt EC. The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study. medRxiv [Preprint]. 2024 Sep 8:2024.04.03.24304759. doi: 10.1101/2024.04.03.24304759.

    PubMed 38633771

  • Huguenard AL, Tan G, Johnson GW, Adamek M, Coxon AT, Kummer TT, Osbun JW, Vellimana AK, Limbrick DD Jr, Zipfel GJ, Brunner P, Leuthardt EC. Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial. medRxiv [Preprint]. 2024 Mar 19:2024.03.18.24304239. doi: 10.1101/2024.03.18.24304239.

    PubMed 38562875

Questions about this trial

What is this clinical trial studying?

A study testing Auricular Vagus Nerve Stimulation in people with Subarachnoid Hemorrhage, run by Anna Huguenard at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Inflammatory markers in the serum on admission (time frame: On hospital day 1). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04557618, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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